The invention relates to a synthetic, statistic thymic peptide combination and its use as an immunologically and endocrinologically active preparation.
From an increasing number of scientific publications, it becomes obvious that a communication exists by means of low-molecular signaling substances between the brain, the organs of the immune system (bone marrow, thymus, lymph nodes, spleen, intestinal mucosa, pulmonary epithelium, and body skin) and the endocrine system of the hormonal control. From the thymic tissue, low-molecular proteins, so-called signaling peptides, were identified, which function both on a neuronal level as neurotransmitters and on an immunological level as differentiation factors.
It was possible to prove in animal experiments that low-molecular signaling peptides are capable of inducing a differentiation cascade in T and B lymphocytes from pluripotent parent cells, when such active peptide substances are subcutaneously supplied to the organism. Moreover, is has been found that such signaling molecules, whose composition corresponds to the proteinic elements of the thymus gland, are capable of protecting the organism against opportunistic infections, when same has previously been harmed, for example, by X-rays, cancer chemotherapy, or a latent virus infection. Such early damage to the regulatory equilibrium of the organism is accompanied by hormonal disorders, which express themselves by changed fertility, reduced mental and physical performance, sleep disorders, and loss of appetite. Moreover, humans exhibit a reduced protective function of the skin as well of the quality of hair and nail growth.
From experience, medical science has countered this syndrome for a long time in that preparations of organic extracts are used as medicines or food supplements. Such preparations of the thymic tissue from animals, in particular thymus of the calf, have found wide use, even when a molecularly defined principle of action of such preparations has not been described until now. Positive data from a series of biological studies in vivo with such thymus preparations permit concluding that substances contained in the thymus tissue exert synergistic effects both on the neuronal and on the immune system. However, in the last five years the risk has come to the fore that such preparations of organic extracts from animals are contaminated with prion proteins. These prion proteins are associated with transmitting the symptoms of BSE (bovine spongiform encephalopathy, xe2x80x9cbovine madnessxe2x80x9d).
It is therefore the object of the present invention to make available an immunologically and/or endocrinologically active preparation, which permits on the one hand extrapolating the positive experience with thymic peptide combinations, but totally excludes on the other hand the risk of BSE. Furthermore, it is the object to specify a synthetic, statistic thymic peptide combination and its use as an immunologically and/or endocrinologically active preparation with corresponding advantages.
The invention provides synthetic thymic peptide combinations in the absence of risk of BSE by synthetically building the peptides characteristic of thymus from chromatographically clarified amino acids. An immunologically and endocrinologically active preparation can be prepared that contains as an active ingredient short-chain peptides characteristic of thymic tissue.
Methods for preparing the synthetic thymus peptide combinations are also provided. These methods include the synthesis of peptides from chemically suitable derivated amino acids while maintaining the weighted quantity ratio and pattern of amino acids characteristics of the thymus tissue. The amino acids are activated for a sequence of reactions in which one active N-terminal group is alternately protected and then deprotected until the discrete peptide sequence is built. Preparations of calf thymus extract obtained by partial hydrolysis of the thymus tissue have been commercially available. In sharp contrast thereto, the synthetic thymus peptides of the invention are prepared by separating the amino acids; functionalizing the amino acids for peptide buliding reactions; reacting the amino acids to build a peptide combination by alternately reacting the amino acids to join them together in a weight ratio characteristics of thymus tissue, deprotecting a remaining reactive group, and again reacting the amino acids to continue building the peptide to the desired products, whereby prions are excluded.
The preparations of the invention, which are synthetic, statistic thymic peptides having a weighted quantity ratio and pattern of amino acids characteristic of thymus tissue and having immunologically and endocrinologically active properties, can be used to treat weak immunity and immunodeficiencies and hormonal disorders, and can be used in the cosmetic field as a nutrient for skin, hair, and nails, and as a dietary supplement in the field of food supplements.
Proceeding from partial hydrolysates of thymic protein, protein mixtures from short-chain thymic peptides and amino acids, which result from an enzymatic and/or chemical partial hydrolysis of thymus tissue, such combinations were clarified by way of chromatography and amino-acid analysis to that extent that the such partial hydrolysates consist of short-chain peptides with a quantity ratio and pattern of amino acid characteristic of thymus tissue. When such amino acids are reacted with one another in chemically suitably derivatized form, with the quantity ratio of the amino acids characteristic of the thymus tissue being maintained, when such synthetic combinations are released from their N-terminal protective groups and coupled again and repeatedly with such weighted combinations of amino acids, which are characteristic of thymus tissues, one will obtain synthetic, statistic thymic peptide combinations to the total exclusion of the prion protein risk.
Thus, the invention discloses relatively simple ways of purposefully producing immunologically and endocrinologically active preparations with an effect of the preparation that is standardizable for the first time.
It is possible to produce such thymic peptide combinations in a pharmaceutically reproducible sterile manner, so that a preparation results in this manner, which depending on the number of repeated statistic synthesis operations consists of a family of signaling thymic peptides characteristic of neurotransmitters and immunologically active signaling molecules. Based on analytical tests in comparison with partial hydrolysis mixtures from natural thymus tissue, it was possible to demonstrate that, within the margin of error of applied analytical methods, synthetic, statistic thymic peptide combinations are comparable in their composition with the natural preparation. From this follows that it was possible to accomplish the object of the present invention to eliminate the BSE risk by synthesizing a thymic peptide combination.
Surprisingly, it has shown that the synthetic preparation of the present invention exhibits in the biological test on human lymphocytes a superior activity with respect to mitogenic co-stimulation (induction of cell proliferation) in comparison with a commercial thymic preparation produced by partial hydrolysis.
Furthermore, it comes as a surprise that the synthetic preparation is capable of binding constituents of the extracellular matrix, a property that had previously to be ascribed only to scleroproteins.